Evidence for an inhibitory immunomodulatory effect of selected antidepressants on rat splenocytes: Possible relevance to depression and hyperactive-immune disorders
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摘要
Antidepressants have been found to possess antiproliferative effect. In the immune system depression may activate pro-inflammatory cytokines. Therefore, the aim of this study was to assess the immunomodulatory activity of antidepressants in naïve rat. Rat splenocytes were activated with con A and treated with paroxetine, sertraline or clomipramine ex vivo. We found that the antidepressants inhibit cell viability and proliferation at IC50 of 5–8 μM of mitogen-stimulated rat splenocytes. This inhibitory effect was accompanied by cell cycle arrest and increase in apoptotic events as assayed by FACS. Moreover, antidepressants decrease the secretion of the TH1 factor — TNFgreek small letter alpha. In addition, the antidepressants reduced the expression of the enzyme cyclooxygenase2 which is involved in inflammation. On the cellular level we show the up-regulation of MAPK death signaling pathway and suppression of the anti-apoptotic factor — Bcl-2. These findings reveal the immunomodulatory effect of the selected antidepressants. These data suggest a novel use of antidepressants or their derivatives.

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